Mammalian spermatozoa have been known to be antigenic for many years. More recently, it has been demonstrated that mammalian sperm contain an antigenic enzyme, which is known as the C.sub.4 isoenzyme of lactate dehydrogenase (LDH-C.sub.4) LDH-C.sub.4 has been isolated in pure crystalline form from mouse testes. Goldberg (1972), J. Biol. Chem. 247:2044-2048. The enzyme has a molecular weight of 140,000 and is composed of four identical C subunits. The amino acid sequence and three-dimensional structure of mouse LDH-C.sub.4 have been studied-described by a number of investigators: Musick, et al. (1976), J. Mol. Biol. 104:659-668; Wheat, et al. (1977), Biochem. & Biophys. Res. Comm. 74, No. 3:1066-1077; Li et al. (1983), J. Biol. Chem. 258:7017-7028; and Pan, et al. (1983), J. Biol. Chem. 258:7005-7016.
In 1974, Dr. Erwin Goldberg reviewed the effects of immunization with LDH-X (LDH-C.sub.4) on fertility, and advanced the possibility that "by using a defined macro-molecular constituent of sperm it becomes possible to elucidate its primary structure in terms of amino acid sequence, to map specifically the antigenic determinant(s) responsible for inducing infertility, and then to construct synthetic peptides containing these determinants. Possessing the capability for synthesizing a molecule with such properties makes the immunological approach to fertility control feasible". Karolinska Symposia on Research Methods in Reproductive Endocrinology 7th Symposium: Immunological Approaches to Fertility Control, Geneva, 1974, 202-222.
Subsequent investigations by Dr. Goldberg and his research associates identified several amino acid sequences of mouse LDH-C.sub.4 which in isolated form (e.g., as short chain peptides) bind to LDH-C.sub.4 antiserum. Wheat, et al. (1981) in Rich, et al., Peptides: Synthesis-Structure-Function, Proc. 7th Amer. Peptide Symp., pp. 557-560; and Gonzales-Prevatt, et al. (1982), Mol. Immunol. 19:1579-1585. Antigenic peptide compounds based on these sequences have been patented. See U.S. Pat. Nos. 4,290,944; 4,310,456; 4,353,822; 4,377,516, 4,392,997; 4,578,219; and 4,585,587.
These antigenic peptides are useful in preparing vaccines to reduce female fertility. Immunization of female mammals results in the development of circulating antibodies specific to LDH-C.sub.4. These immunoglobulins reach the female reproductive tract as a transudate of serum. Kille, et al. (1977), Biol. Reprod. 20:863-871. Antibody in cervical mucus, uterine fluids, and oviducal fluids combine with LDH-C.sub.4 on the sperm surface and impede the progress of the male gamete, presumably by agglutination. Systemic immunization with LDH-C.sub.4 markedly interferes with sperm transport in the female reproductive tract. Kille et al. (1980), J. Reprod. Immunol. 2:15-21.
The current status of research on LDH-C.sub.4 and antigenic peptides for use in female contraceptive vaccines is summarized in two recent publications by the Goldberg group: Goldberg, et al. (1983) In Immunology of Reproduction, Chapt. 22, pp. 493-504; and Wheat, et al. (1983), in Isozymes: Current Topics in Biological and Medical Research, Vol. 7, pp. 113-140.
In the prior work on synthetic antigenic peptides corresponding to antigenic regions of LDH-C.sub.4, it was assumed that the antigenic regions of mouse LDH-C.sub.4 enzyme were essentially homologous with those of human LDH-C.sub.4. Tests in female rabbits had demonstrated immunization effects from the mouse antigenic sequences. The synthetic peptide corresponding to the mouse LDH-C.sub.4 sequence 5-15 was found to be antigenic for immunizing not only female rabbits but also female baboons. See Goldberg and Shelton, in "Immunological Approaches to Contraception and Promotion of Fertility", pages 219-230 (ed. G. P. Talwar, Plenum Publishing Corp., 1986).